chr22-41943521-G-A

Variant names:

• chr22-41943521-G-A
• rs10483213
• NM_024053.5:c.402+89C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024053.5(CENPM):​c.402+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 1,140,410 control chromosomes in the GnomAD database, including 4,070 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (419 hom., cov: 32)
  • Exomes 𝑓: 0.081 (3651 hom.)
• Consequence: CENPM NM_024053.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 19 publications found

Genes affected

CENPM (HGNC:18352): (centromere protein M) The protein encoded by this gene is an inner protein of the kinetochore, the multi-protein complex that binds spindle microtubules to regulate chromosome segregation during cell division. It belongs to the constitutive centromere-associated network protein group, whose members interact with outer kinetochore proteins and help to maintain centromere identity at each cell division cycle. The protein is structurally related to GTPases but cannot bind guanosine triphosphate. A point mutation that affects interaction with another constitutive centromere-associated network protein, CENP-I, impairs kinetochore assembly and chromosome alignment, suggesting that it is required for kinetochore formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024053.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPM	NM_024053.5	MANE Select	c.402+89C>T		intron	N/A	NP_076958.1
	CENPM	NM_001304370.2		c.300+89C>T		intron	N/A	NP_001291299.1
	CENPM	NM_001304372.2		c.*7+89C>T		intron	N/A	NP_001291301.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPM	ENST00000215980.10	TSL:1 MANE Select	c.402+89C>T		intron	N/A	ENSP00000215980.5
	CENPM	ENST00000718240.1		c.300+89C>T		intron	N/A	ENSP00000520685.1
	CENPM	ENST00000402338.5	TSL:2	c.300+89C>T		intron	N/A	ENSP00000384731.1

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9905 AN: 152110 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.0618

GnomAD4 exome AF: 0.0808 AC: 79863 AN: 988182 Hom.: 3651 AF XY: 0.0809 AC XY: 40257 AN XY: 497846

African (AFR) AF: 0.0136 AC: 321 AN: 23542

American (AMR) AF: 0.0374 AC: 1213 AN: 32406

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 1784 AN: 20372

East Asian (EAS) AF: 0.000236 AC: 8 AN: 33902

South Asian (SAS) AF: 0.0424 AC: 2670 AN: 63014

European-Finnish (FIN) AF: 0.109 AC: 5262 AN: 48360

Middle Eastern (MID) AF: 0.0786 AC: 270 AN: 3436

European-Non Finnish (NFE) AF: 0.0908 AC: 65287 AN: 719128

Other (OTH) AF: 0.0692 AC: 3048 AN: 44022

GnomAD4 genome AF: 0.0650 AC: 9902 AN: 152228 Hom.: 419 Cov.: 32 AF XY: 0.0639 AC XY: 4756 AN XY: 74422

African (AFR) AF: 0.0161 AC: 667 AN: 41538

American (AMR) AF: 0.0447 AC: 683 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0390 AC: 188 AN: 4818

European-Finnish (FIN) AF: 0.115 AC: 1219 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6555 AN: 68010

Other (OTH) AF: 0.0611 AC: 129 AN: 2110

Alfa AF: 0.0796 Hom.: 1079

Bravo AF: 0.0575

Asia WGS AF: 0.0190 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	0.74
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10483213; hg19: chr22-42339525; COSMIC: COSV53245050; COSMIC: COSV53245050;